Bei Prototype 2 wird der Spieler mitten in das Zombie verseuchte New York City versetzt. Dort kann er sich völlig frei bewegen. In den Stiefeln von Sergeant Heller schlägt sich der Spieler in einzigartiger Prototype-Manier durch Horden angriffslustiger Mutanten und erlebt Action in einer völlig neuen Dimension! Englische Sprachausgabe: This time out you play Sgt. James Heller, a soldier on his way back from tours of Afghanistan and Iraq. Before he makes it home, however, tragedy strikes and there's a second outbreak of what's now known as the Mercer Virus. He finds his family dead at the hands of virus victims and blames Alex Mercer, who's thought to be spreading the disease. When Heller's mortally wounded and revived by Mercer – gaining shape-shifting powers in the process – things get decidedly more complicated...